PXD035189

PXD035189 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1
Description	RNA splicing, the process of intron removal from pre-mRNA, is essential for the regulation of gene expression. It is controlled by the spliceosome, a megadalton RNA-protein complex that assembles de novo on each pre-mRNA intron via an ordered assembly of intermediate complexes. Spliceosome activation is a major control step requiring dramatic protein and RNA rearrangements leading to a catalytically active complex. Splicing factor 3B subunit 1 (SF3B1) protein, a subunit of the U2 snRNP, is phosphorylated during spliceosome activation, but the responsible kinase has not been identified. Here we show that cyclin-dependent kinase 11 (CDK11) associates with SF3B1 and phosphorylates threonine residues at its N-terminus during spliceosome activation. The phosphorylation is important for association of SF3B1 with U5 and U6 snRNAs in spliceosome activated Bact complex and it can be blocked by OTS964, a potent and selective inhibitor of CDK11. CDK11 inhibition prevents spliceosomal transition from the precatalytic complex B to the activated complex Bact and leads to widespread intron retention and accumulation of non-functional spliceosomes on pre-mRNAs and chromatin. We characterize OTS964 as a quality chemical biology probe for CDK11 and demonstrate a central role of CDK11 in spliceosome assembly and splicing regulation.
HostingRepository	MassIVE
AnnounceDate	2022-07-09
AnnouncementXML	Submission_2022-07-09_05:54:07.186.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Potesil
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Phospho
Instrument	impact II; timsTOF Pro

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-09 05:17:57	ID requested
⏵ 1	2022-07-09 05:54:07	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: CDK11, kinase, phosphorylation, PTM, LC-MS

submitter keyword: CDK11, kinase, phosphorylation, PTM, LC-MS

Contact List

Dalibor Blazek
contact affiliation	CEITEC
contact email	dalibor.blazek@ceitec.muni.cz
lab head
David Potesil
contact affiliation	CEITEC
contact email	david.potesil@ceitec.muni.cz
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000089855/